Adam J. Krieg, Ph.D.

  • Assistant Professor of Obstetrics and Gynecology, School of Medicine
  • Affiliate Assistant Professor, Oregon National Primate Research Center

Biography

Dr. Adam Krieg is an Assistant Professor of Obstetrics and Gynecology in the division of Gynecologic Oncology. He holds an affiliate appointment with the Oregon National Primate Research Center in the Division of Reproductive and Developmental Sciences.

Dr. Krieg’s research team studies the role of reduced tissue oxygen (hypoxia) as a factor in tumor progression and normal physiological processes. Dr. Krieg is investigating how various hypoxia-regulated genes contribute to therapeutic response and resistance in gynecological cancers, especially high-grade serous ovarian carcinoma, the most common and deadly of ovarian cancers. More recently, Dr. Krieg has been working with other members of the OHSU gynecological oncology division to develop a program to study how rare mutations in the SMARCA4 tumor suppressor lead to transformation of ovarian cells to form Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT), a very rare but deadly ovarian cancer that afflicts young women.

Many hypoxia-regulated genes, such as SMARCA4 and the class of epigenetic regulators called histone demethylases, are also highly expressed in normal reproductive tissues and may contribute to human fertility. To that end, Dr. Krieg is using both human and non-human primate models of ovarian biology to investigate the role of oxygen, hypoxia-regulated genes, SMARCA4, and histone demethylases in influencing normal ovarian processes and infertility. Related to these interests, Dr. Krieg is also researching the contribution of Anti-Mullerian Hormone to the maintenance of ovarian reserve and preservation of reproductive function.

Dr. Krieg received his Ph.D. in Biochemistry from the University of Illinois, Urbana-Champaign in 2003. As a postdoctoral fellow in the department of Radiation Oncology at Stanford University, he conducted research in hypoxic gene expression mechanisms. In 2010, he continued his studies as an assistant professor of OB/GYN at the University of Kansas Medical Center. He joined the faculty of Obstetrics and Gynecology at OHSU as an assistant professor in 2016.

Education and training

  • Degrees

    • B.S., 1995, Oregon State University
    • Ph.D., 2003, University of Illinois, Urbana-Champaign

  • Fellowship

    • Postdoctoral Fellow, Radiation and Cancer Biology, Stanford University. 2003-2010

Areas of interest

  • Gene expression and epigenetic regulation
  • Tumor hypoxia
  • Low oxygen biology
  • Ovarian and Gynecological Cancers
  • Infertility
  • Reproductive physiology

Additional information

Honors and awards

  • Junior Investigator. NIH/Kansas COBRE Molecular Regulation of Cell Development and Differentiation (2010-2013)
  • Ruth L. Kirchstein NIH National Research Service Award (2008-2010)
  • University of Illinois NIH Reproductive Biology Predoctoral Training Grant (1998–2000)
  • University of Illinois NIH Cell and Molecular Biology Predoctoral Training Grant (1995–1998)
  • Oregon State University Jesse Hanson College of Science Scholarship (1992–1995)
  • Oregon State University Presidential Scholarship (1991–1995)
  • Molalla, OR Rotary Scholarship (1991–1995)

Publications

Selected publications

  • Licofelone enhances the efficacy of paclitaxel in ovarian cancer by reversing drug resistance and tumor stem-like properties. Hirst J, Pathak HB, Hyter S, Pessetto ZY, Ly T, Graw S, Koestler DC, Krieg AJ, Roby KF, Godwin AK. Cancer Res. 2018 Jun 11. pii: canres.3993.2017. doi: 10.1158/0008-5472.CAN-17-3993. [Epub ahead of print]. PMID: 29891506.
  • Histone demethylase KDM4A and KDM4B expression in granulosa cells from women undergoing in vitro fertilization. Krieg AJ, Mullinax SR, Grimstad F, Marquis K, Constance E, Hong Y, Krieg SA, Roby KF. J Assist Reprod Genet. 2018 Jun;35(6):993-1003. doi: 10.1007/s10815-018-1151-3. Epub 2018 Mar 14. PMID: 29536385.
  • KDM4A regulates HIF-1 levels through H3K9me3. Dobrynin G, McAllister TE, Leszczynska KB, Ramachandran S, Krieg AJ, Kawamura A, Hammond EM. Sci Rep. 2017 Sep 11;7(1):11094. doi: 10.1038/s41598-017-11658-3. PMID: 28894274.
  • Genome-independent hypoxic repression of estrogen receptor alpha in breast cancer cells. Padró M, Louie RJ, Lananna BV, Krieg AJ, Timmerman LA, Chan DA. BMC Cancer. 2017 Mar 20;17(1):203. doi: 10.1186/s12885-017-3140-9. PMID: 28320353.
  • KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. Castellini L, Moon EJ, Razorenova OV, Krieg AJ, von Eyben R, Giaccia AJ. Nucleic Acids Res. 2017 Apr 20;45(7):3674-3692. doi: 10.1093/nar/gkw1281. PMID: 28073943.
  • The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer. Wilson C, Qiu L, Hong Y, Karnik T, Tadros G, Mau B, Ma T, Mu Y, New J, Louie RJ, Gunewardena S, Godwin AK, Tawfik OW, Chien J, Roby KF, Krieg AJ. Oncogene. 2017 May 4;36(18):2565-2576. doi: 10.1038/onc.2016.412. Epub 2016 Nov 21. PMID: 27869162.
  • HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia. Chakraborty D, Cui W, Rosario GX, Scott RL, Dhakal P, Renaud SJ, Tachibana M, Rumi MA, Mason CW, Krieg AJ, Soares MJ. Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):E7212-E7221. Epub 2016 Nov 2. PMID: 27807143.
  • Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia. Ramachandran S, Ient J, Göttgens EL, Krieg AJ, Hammond EM. Genes (Basel). 2015 Sep 25;6(4):935-56. doi: 10.3390/genes6040935. Review. PMID: 26426056.
  • Hypoxic induction of AKAP12 variant 2 shifts PKA-mediated protein phosphorylation to enhance migration and metastasis of melanoma cells. Finger EC, Castellini L, Rankin EB, Vilalta M, Krieg AJ, Jiang D, Banh A, Zundel W, Powell MB, Giaccia AJ. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4441-6. doi: 10.1073/pnas.1418164112. Epub 2015 Mar 19. PMID: 25792458.
  • Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Rankin EB, Fuh KC, Castellini L, Viswanathan K, Finger EC, Diep AN, LaGory EL, Kariolis MS, Chan A, Lindgren D, Axelson H, Miao YR, Krieg AJ, Giaccia AJ. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13373-8. doi: 10.1073/pnas.1404848111. Epub 2014 Sep 3. PMID: 25187556.
  • Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes. Taniguchi CM, Finger EC, Krieg AJ, Wu C, Diep AN, LaGory EL, Wei K, McGinnis LM, Yuan J, Kuo CJ, Giaccia AJ. Nat Med. 2013 Oct;19(10):1325-30. doi: 10.1038/nm.3294. Epub 2013 Sep 15. PMID: 24037093
  • Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss. Krieg SA, Fan X, Hong Y, Sang QX, Giaccia A, Westphal LM, Lathi RB, Krieg AJ, Nayak NR. Mol Hum Reprod. 2012 Sep;18(9):442-50. doi: 10.1093/molehr/gas017. Epub 2012 Apr 14. PMID: 22505054
  • VHL loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKC{delta}-driven migration. Razorenova OV, Finger EC, Colavitti R, Chernikova SB, Boiko AD, Chan CK, Krieg A, Bedogni B, LaGory E, Weissman IL, Broome-Powell M, Giaccia AJ. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1931-6. doi: 10.1073/pnas.1011777108. Epub 2011 Jan 13. PMID: 21233420
  • AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Rankin EB, Fuh KC, Taylor TE, Krieg AJ, Musser M, Yuan J, Wei K, Kuo CJ, Longacre TA, Giaccia AJ. Cancer Res. 2010 Oct 1;70(19):7570-9. doi: 10.1158/0008-5472.CAN-10-1267. Epub 2010 Sep 21. PMID: 20858715
  • Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Krieg AJ, Rankin EB, Chan D, Razorenova O, Fernandez S, Giaccia AJ. Mol Cell Biol. 2010 Jan;30(1):344-53. doi: 10.1128/MCB.00444-09. PMID: 19858293
  • The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation. Basak S, Jacobs SB, Krieg AJ, Pathak N, Zeng Q, Kaldis P, Giaccia AJ, Attardi LD. Mol Cell. 2008 May 9;30(3):303-14. doi: 10.1016/j.molcel.2008.04.002. PMID: 18471976
  • HIF gene expression in cancer therapy. Chan DA, Krieg AJ, Turcotte S, Giaccia AJ. Methods Enzymol. 2007;435:323-45. Review. PMID: 17998061
  • Targeting the loss of the von Hippel-Lindau tumor suppressor gene in renal cell carcinoma cells. Sutphin PD, Chan DA, Li JM, Turcotte S, Krieg AJ, Giaccia AJ. Cancer Res. 2007 Jun 15;67(12):5896-905. PMID: 17575159
  • Functional analysis of p53 binding under differential stresses. Krieg AJ, Hammond EM, Giaccia AJ. Mol Cell Biol. 2006 Oct;26(19):7030-45. PMID: 16980608
  • Checking in on hypoxia/reoxygenation. Freiberg RA, Krieg AJ, Giaccia AJ, Hammond EM. Cell Cycle. 2006 Jun;5(12):1304-7. Epub 2006 Jun 15. Review. PMID: 16760660
  • Genome-wide analysis of p53 under hypoxic conditions. Hammond EM, Mandell DJ, Salim A, Krieg AJ, Johnson TM, Shirazi HA, Attardi LD, Giaccia AJ. Mol Cell Biol. 2006 May;26(9):3492-504. PMID: 16611991
  • Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes. Krieg AJ, Krieg SA, Ahn BS, Shapiro DJ. J Biol Chem. 2004 Feb 6;279(6):5025-34. Epub 2003 Nov 14. PMID: 14617632
  • A unique downstream estrogen responsive unit mediates estrogen induction of proteinase inhibitor-9, a cellular inhibitor of IL-1beta- converting enzyme (caspase 1). Krieg SA, Krieg AJ, Shapiro DJ. Mol Endocrinol. 2001 Nov;15(11):1971-82. PMID: 11682627
  • Interactions of high mobility group box proteins with DNA and chromatin. Churchill ME, Changela A, Dow LK, Krieg AJ. Methods Enzymol. 1999;304:99-133. PMID: 10372358

Publications